Development and stability analysis of carpal kinematic metrics from 4D magnetic resonance imaging.

OBJECTIVE: To develop MRI-derived carpal kinematic metrics and investigating their stability. METHODS: The study used a 4D MRI method to track scaphoid, lunate, and capitate movements in the wrist. A panel of 120 metrics for radial-ulnar deviation and flexion-extension was created using polynomial models of scaphoid and lunate movements relative to the capitate. Intraclass correlation coefficients (ICCs) analyzed intra- and inter-subject stability in 49 subjects, 20 with and 29 without wrist injury history. RESULTS: Comparable degrees of stability were observed across the two different wrist movements. Among the total 120 derived metrics, distinct subsets demonstrated high stability within each type of movement. For asymptomatic subjects, 16 out of 17 metrics with high intra-subject stability also showed high inter-subject stability. The differential analysis of ICC values for each metric between asymptomatic and symptomatic cohorts revealed specific metrics (although relatively unstable) exhibiting greater variability in the symptomatic cohort, thereby highlighting the impact of wrist conditions on the variability of kinematic metrics. CONCLUSION: The findings demonstrate the developing potential of dynamic MRI for assessing and characterizing complex carpal bone dynamics. Stability analyses of the derived kinematic metrics revealed encouraging differences between cohorts with and without wrist injury histories. Although these broad metric stability variations highlight the potential utility of this approach for analyzing carpal instability, further studies are necessary to better characterize these observations.

Split-slice training and hyperparameter tuning of RAKI networks for simultaneous multi-slice reconstruction.

PURPOSE: Simultaneous multi-slice acquisitions are essential for modern neuroimaging research, enabling high temporal resolution functional and high-resolution q-space sampling diffusion acquisitions. Recently, deep learning reconstruction techniques have been introduced for unaliasing these accelerated acquisitions, and robust artificial-neural-networks for k-space interpolation (RAKI) have shown promising capabilities. This study systematically examines the impacts of hyperparameter selections for RAKI networks, and introduces a novel technique for training data generation which is analogous to the split-slice formalism used in slice-GRAPPA. METHODS: RAKI networks were developed with variable hyperparameters and with and without split-slice training data generation. Each network was trained and applied to five different datasets including acquisitions harmonized with Human Connectome Project lifespan protocol. Unaliasing performance was assessed through L1 errors computed between unaliased and calibration frequency-space data. RESULTS: Split-slice training significantly improved network performance in nearly all hyperparameter configurations. Best unaliasing results were achieved with three layer RAKI networks using at least 64 convolutional filters with receptive fields of 7 voxels, 128 single-voxel filters in the penultimate RAKI layer, batch normalization, and no training dropout with the split-slice augmented training dataset. Networks trained without the split-slice technique showed symptoms of network over-fitting. CONCLUSIONS: Split-slice training for simultaneous multi-slice RAKI networks positively impacts network performance. Hyperparameter tuning of such reconstruction networks can lead to further improvements in unaliasing performance.

Multispectral diffusion-weighted MRI of the instrumented cervical spinal cord: a preliminary study of 5 cases.

PURPOSE: Diffusion-weighted imaging has undergone substantial investigation as a potential tool for advanced assessment of spinal cord health. Unfortunately, commonly encountered surgically implanted spinal hardware has historically disrupted these studies. This preliminary investigation applies the recently developed multispectral diffusion-weighted PROPELLER technique to quantitative assessment of the spinal cord immediately adjacent to metallic spinal fusion instrumentation. METHODS: Morphological and diffusion-weighted MRI of the spinal cord was collected from 5 subjects with implanted cervical spinal fusion hardware. Conventional and multispectral diffusion-weighted images were also collected on a normative non-instrumented control cohort and utilized for methodological stability analysis. Variance of the ADC values derived from the normative control group was then analyzed on a subject-by-subject basis and qualitatively correlated with clinical morphological interpretations. RESULTS: Normative control ADC values within the spinal cord were stable across DWI methods for a b value of 600 s/mm2, though this stability degraded at lower b value levels. Susceptibility artifacts precluded conventional DWI analysis of the cord in subjects with spinal fusion hardware in 4 of the 5 test cases. On the contrary, multispectral PROPELLER DWI produced viable ADC measurements within the cord of all 5 instrumented subjects. Instrumented cord regions without obvious pathology (N = 4) showed ADC values that were lower than expected, whereas one subject with diagnosed myelomalacia showed abnormally elevated ADC. CONCLUSIONS: In the absence of instrumentation, multispectral DWI provides quantitative capabilities that match with those of conventional DWI approaches. In a preliminary instrumented subject analysis, cord ADC values showed both expected and unexpected variations from the normative cohort. These slides can be retrieved under Electronic Supplementary Material.

3D-multi-spectral T2 mapping near metal implants.

PURPOSE: Due to host-mediated adverse reaction to metallic debris, there is an increasing need for noninvasive assessment of the soft tissue surrounding large joint arthroplasties. Quantitative T2 mapping can be beneficial for tissue characterization and early diagnosis of tissue pathology but current T2 mapping techniques lack the capability to image near metal hardware. A novel multi-spectral T2 mapping technique is proposed to address this unmet need. METHODS: A T2 mapping pulse sequence based on routinely implemented 3D multi-spectral imaging (3D-MSI) pulse sequences is described and demonstrated. The 3D-MSI pulse sequence is altered to acquire images at 2 echo times. Phantom and knee experiments were performed to assess the quantitative capabilities of the sequence in comparison to a commercially available T2 mapping sequence. The technique was demonstrated for use within a clinical protocol in 2 total hip arthroplasty (THA) cases to assess T2 variations within the periprosthetic joint space. RESULTS: The proposed multi-spectral T2 mapping technique agreed, within experimental errors, with T2 values derived from a commercially available clinical standard of care T2 mapping sequence. The same level of agreement was observed in quantitative phantoms and in vivo experiments. In THA cases, the method was able to assess variations of T2 within the synovial envelope immediately adjacent to implant interfaces. CONCLUSIONS: The proposed 3D-MSI T2 mapping sequence was successfully demonstrated in assessing tissue T2 variations near metal implants.

Fully phase-encoded MRI near metallic implants using ultrashort echo times and broadband excitation.

PURPOSE: To develop a fully phase-encoded MRI method for distortion-free imaging near metallic implants, in clinically feasible acquisition times. THEORY AND METHODS: An accelerated 3D fully phase-encoded acquisition with broadband excitation and ultrashort echo times is presented, which uses a broadband radiofrequency pulse to excite the entire off-resonance induced by the metallic implant. Furthermore, fully phase-encoded imaging is used to prevent distortions caused by frequency encoding, and to obtain ultrashort echo times for rapidly decaying signal. RESULTS: Phantom and in vivo acquisitions were used to describe the relationship among excitation bandwidth, signal loss near metallic implants, and T1 weighting. Shorter radiofrequency pulses captured signal closer to the implant by improving spectral coverage and allowing shorter echo times, whereas longer pulses improved T1 weighting through larger maximum attainable flip angles. Comparisons of fully phase-encoded acquisition with broadband excitation and ultrashort echo times to T1 -weighted multi-acquisition with variable resonance image combination selective were performed in phantoms and subjects with metallic knee and hip prostheses. These acquisitions had similar contrast and acquisition efficiency. CONCLUSIONS: Accelerated fully phase-encoded acquisitions with ultrashort echo times and broadband excitation can generate distortion free images near metallic implants in clinically feasible acquisition times. Magn Reson Med 79:2156-2163, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Multispectral diffusion-weighted imaging near metal implants.

PURPOSE: The need for diffusion-weighted-imaging (DWI) near metallic implants is becoming increasingly relevant for a variety of clinical diagnostic applications. Conventional DWI methods are significantly hindered by metal-induced image artifacts. A novel approach relying on multispectral susceptibility artifact reduction techniques is presented to address this unmet need. METHODS: DWI near metal implants is achieved through a combination of several advanced MRI acquisition technologies. Previously described approaches to Carr-Purcell-Meiboom-Gill spin-echo train DWI sequences using the periodically rotated overlapping parallel lines with enhanced reconstruction are combined with multispectral-imaging metal artifact reduction principles to provide DWI with substantially reduced artifact levels. The presented methods are applied to limited sets of slices over areas of sarcoma risk near six implanted devices. RESULTS: Using the presented methods, DWI assessment without bulk image distortions is demonstrated in the immediate vicinity of metallic interfaces. In one subject, the apparent diffusion coefficient was reduced in a region of suspected sarcoma directly adjacent to fixation hardware. CONCLUSIONS: An initial demonstration of minimal-artifact multispectral DWI in the near vicinity of metallic hardware is described and successfully demonstrated on clinical subjects. Magn Reson Med 79:987-993, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Off-resonance based assessment of metallic wear debris near total hip arthroplasty.

PURPOSE: The presence of metallic debris near total hip arthroplasty can have a significant impact on longitudinal patient management. Methods for magnetic resonance imaging-based quantification of metallic debris near painful total hip replacements are described and applied to cohorts of symptomatic and control subject cases. METHODS: A combination of metal artifact reduction, off-resonance mapping, off-resonance background removal, and spatial clustering methods are utilized to quantify off-resonance signatures in cases of suspected metallosis. These methods are applied to a cohort of symptomatic hip arthroplasties composed of cobalt-chromium alloys. Magnetostatic simulations and theoretical principles are used to illuminate the potential sources of the measured off-resonance effects. Reported metrics from histological tissue assays extracted during surgical revision procedures are also correlated with the proposed magnetic resonance imaging-based quantification results. RESULTS: The presented methods identified quantifiable metallosis signatures in more than 70% of the symptomatic and none of the control cases. Preliminary correlations of the MR data with direct histological evaluation of retrieved tissue samples indicate that the observed off-resonance effect may be related to tissue necrosis. CONCLUSIONS: Magnetostatic simulations, theoretical principles, and preliminary histological trends suggest that disassociated cobalt is the source of the observed off-resonance signature. Magn Reson Med 79:1628-1637, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Peripheral nerve diffusion tensor imaging: Overview, pitfalls, and future directions.

Diffusion tensor imaging (DTI) is a noninvasive magnetic resonance imaging (MRI) technique that measures the extent of restricted water diffusion and anisotropy in biological tissue. Although DTI has been widely applied in the brain, more recently researchers have used it to characterize nerve pathology in the setting of entrapment neuropathy, traumatic injury, and tumor. DTI artifacts are exacerbated when imaging off isocenter in the body. Anecdotally, the most significant artifacts in peripheral nerve DTI include magnetic field inhomogeneity, motion, incomplete fat suppression, aliasing, and distortion. High spatial resolution is also required to reliably evaluate smaller peripheral nerves. This article provides an overview of such technical issues, particularly when trying to apply DTI in the clinical setting, and offers potential solutions. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1171-1189.

Metallic implant geometry and susceptibility estimation using multispectral B0 field maps.

PURPOSE: To estimate the susceptibility and the geometry of metallic implants from multispectral imaging (MSI) information, to separate the metal implant region from the surrounding signal loss region. THEORY AND METHODS: The susceptibility map of signal-void regions is estimated from MSI B0 field maps using total variation (TV) regularized inversion. Voxels with susceptibility estimates above a predetermined threshold are identified as metal. The accuracy of the estimated susceptibility and implant geometry was evaluated in simulations, phantom, and in vivo experiments. RESULTS: The proposed method provided more accurate susceptibility estimation compared with a previous method without TV regularization, in both simulations and phantom experiments. In the phantom experiment where the actual implant was 40% of the signal-void region, the mean estimated susceptibility was close to the susceptibility in literature, and the precision and recall of the estimated geometry was 85% and 93%. In vivo studies in subjects with hip implants also demonstrated that the proposed method can distinguish implants from surrounding low-signal tissues, such as cortical bone. CONCLUSION: The proposed method can improve the delineation of metallic implant geometry by distinguishing metal voxels from artificial signal voids and low-signal tissues by estimating the susceptibility maps. Magn Reson Med 77:2402-2413, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Imaging near orthopedic hardware.

Over one million total joint replacement surgeries were performed in the US in 2013 alone, and this number is expected to more than double by 2030. Traditional imaging techniques for postoperative evaluation of implanted devices, such as radiography, computerized tomography, or ultrasound, utilize ionizing radiation, suffer from beam hardening artifact, or lack the inherent high contrast necessary to adequately evaluate soft tissues around the implants, respectively. Magnetic resonance imaging (MRI), due to its ability to generate multiplanar, high-contrast images without the use of ionizing radiation is ideal for evaluating periprosthetic soft tissues but has traditionally suffered from in-plane and through-plane data misregistration due to the magnetic susceptibility of implanted materials. A recent renaissance in the interest of imaging near arthroplasty and implanted orthopedic hardware has led to the development of new techniques that help to mitigate the effects of magnetic susceptibility. This article describes the challenges of performing imaging near implanted orthopedic hardware, how to generate clinically interpretable images when imaging near implanted devices, and how the images may be interpreted for clinical use. We will also describe current developments of utilizing MRI to evaluate implanted orthopedic hardware. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:24-39.

Quantifying metal-induced susceptibility artifacts of the instrumented spine at 1.5T using fast-spin echo and 3D-multispectral MRI.

PURPOSE: To evaluate magnetic resonance imaging (MRI) artifacts near metallic spinal instrumentation using both conventional metal artifact reduction sequences (MARS) and 3D multispectral imaging sequences (3D-MSI). MATERIALS AND METHODS: Both MARS and 3D-MSI images were acquired in 10 subjects with titanium spinal hardware on a 1.5T GE 450W scanner. Clinical computed tomography (CT) images were used to measure the volume of the implant using seed-based region growing. Using 30-40 landmarks, the MARS and 3D-MSI images were coregistered to the CT images. Three independent users manually segmented the artifact volume from both MR sequences. For five L-spine subjects, one user independently segmented the nerve root in both MARS and 3D-MSI images. RESULTS: For all 10 subjects, the measured artifact volume for the 3D-MSI images closely matched that of the CT implant volume (absolute error: 4.3 ± 2.0 cm3 ). The MARS artifact volume was ∼8-fold higher than that of the 3D-MSI images (30.7 ± 20.2, P = 0.002). The average nerve root volume for the MARS images was 24 ± 7.3% lower than the 3D-MSI images (P = 0.06). CONCLUSION: Compared to 3D-MSI images, the higher-resolution MARS images may help study features farther away from the implant surface. However, the MARS images retained substantial artifacts in the slice-dimension that result in a larger artifact volume. These artifacts have the potential to obscure physiologically relevant features, and can be mitigated with 3D-MSI sequences. Hence, MR study protocols may benefit with the inclusion both MARS and 3D-MSI sequences to accurately study pathology near the spine. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:51-58.

External calibration of the spectral coverage for three-dimensional multispectral MRI.

PURPOSE: By combining images created at distinct frequency offsets from the Larmor frequency, three-dimensional (3D) multispectral imaging (3D-MSI) sequences help overcome the large spatial frequency dispersion caused by metal implants. This frequency dispersion, however, varies with the implant size, orientation, and composition. Using a MAVRIC 3D-MSI acquisition, we sought to prospectively calibrate the spectral coverage needed for 3D-MSI scans. This calibration should offer a significant improvement to image quality, and reduce the scan time. METHODS: The 24 spectral bins from the calibration scan were used to generate a map of frequency offsets around the implant. The magnitude image was used to remove any outliers in the associated frequency offset map, and this processed map was used to determine the cutoff frequency offset and, hence, number of spectral bins. This approach was tested in 13 subjects, by retrospectively reconstructing MAVRIC-SL images with fewer spectral bins. Subsequently, the spectral coverage for MAVRIC-SL images was prospectively calibrated in six subjects, and based on the cutoff frequency offset, these images were acquired with fewer spectral bins. RESULTS: With fewer spectral bins, both retrospectively and prospectively calibrated MAVRIC-SL images adequately delineated the implant boundary. CONCLUSION: Incorporating this calibration procedure into future 3D-MSI exams will help improve image signal-to-noise ratio, reduce scan time, and significantly improve clinical workflow when imaging near orthopedic implants. Magn Reson Med 76:1494-1503, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

Flexible longitudinal magnetization contrast in spectrally overlapped 3D-MSI metal artifact reduction sequences: Technical considerations and clinical impact.

PURPOSE: It has previously been demonstrated that increased overlap of spectral bins in three-dimensional multispectral imaging techniques (3D-MSI) can aid in reducing residual artifacts near metal implants. However, increasing spectral overlap also necessitates consideration of saturation effects for species with long T1 values. Here, an interleaved spectral bin acquisition strategy is presented for overlapping 3D-MSI that allows for flexible choice of repetition times while simultaneously addressing these cross talk concerns. METHODS: A phantom imaging experiment is used to illustrate the amplified effect of cross talk on 3D-MSI acquisitions. A methodological approach to address cross talk across a variety of prescribed repetition times is then described. Using the presented principles, a clinical subject with a total hip replacement was imaged to generate T1, proton density, and short-tau inversion recovery contrasts. In addition, a fracture instrumentation case was imaged pre- and postcontrast using T1-weighted spectrally overlapped 3D-MSI. RESULTS: Phantom results demonstrate that conventional spectral interleaving approaches can generate unwanted signal characteristics in heavily overlapped 3D-MSI. Clinical images using the presented methods successfully demonstrate T1, proton density, and inversion recovery image contrasts using heavily overlapped 3D-MSI. CONCLUSIONS: Through automated management of spectral bin distributions across multiple interleaves, a variety of longitudinal magnetization contrasts can efficiently be acquired without any clinically relevant cross-talk impact using heavily overlapped 3D-MSI.

Metal artefact suppression at 3 T MRI: comparison of MAVRIC-SL with conventional fast spin echo sequences in patients with Hip joint arthroplasty.

OBJECTIVE: The aim of our study was to evaluate the clinical feasibility and diagnostic value of a new MRI metal artefact reduction pulse sequence called MAVRIC-SL in a 3 T MRI environment. SUBJECTS AND METHODS: Two MAVRIC-SL sequences obtained in 61 patients with symptomatic total hip replacement were compared with standard FSE-STIR sequences optimized for imaging around metal. Artefact size was measured on the slice of greatest extent. Image quality, fat saturation, image distortion, visibility of anatomical structures, and detectability of joint abnormalities were visually assessed and graded on qualitative scales. Differences between MAVRIC-SL and FSE sequences were tested with the Wilcoxon signed-rank test. RESULTS: MAVRIC-SL sequences at 3 T showed significantly smaller metal artefacts compared to FSE-STIR sequences (p < 0.0001). The general image quality of MAVRIC-SL sequences was reduced with regard to spatial resolution, noise and contrast (p = 0.001), and fat saturation (p < 0.0001). The reduction of artefact size and image distortion significantly improved visualization of joint anatomy (p < 0.0001) and diagnostic confidence regarding implant-associated abnormalities (p = 0.0075 to <0.0001). CONCLUSION: Although the image quality of MAVRIC-SL sequences is limited at 3 T, its clinical application is feasible and provides important additional diagnostic information for the workup of patients with symptomatic hip replacement through substantially reduced metal artefacts. KEY POINTS: • Metal artefacts compromise imaging of total hip replacement with MRI. • Metal artefacts are aggravated with 3 Tesla MRI. • MAVRIC-SL is a technique to suppress metal artefacts. • MAVRIC-SL effectively reduces metal artefacts at 3 Tesla and improves diagnostic quality.

Metal artifact reduction with MAVRIC SL at 3-T MRI in patients with hip arthroplasty.

OBJECTIVE: The objective of our study was to compare the multiacquisition variable-resonance image combination selective (MAVRIC SL) sequence with the 2D fast spin-echo (FSE) sequence for metal artifact reduction on 3-T MRI in patients with hip arthroplasty (HA). MATERIALS AND METHODS: Matched 2D FSE and MAVRIC SL images of 21 hips (19 patients with HA) were included in the study group. Paired image sets, composed of 13 coronal and 12 axial slices (total, 25 image sets), of the 21 hips were evaluated. For quantitative analysis, the artifact area was measured at the level of the hip and femur. For qualitative analysis, two musculoskeletal radiologists independently compared paired 2D FSE and MAVRIC SL sets in terms of artifacts, depiction of anatomic detail, level of diagnostic confidence, and detection of abnormal findings. RESULTS: The measured artifact area was significantly smaller (p < 0.05) on MAVRIC SL than 2D FSE at both the level of hip (59.9% reduction with MAVRIC SL) and femur (31.3% reduction with MAVRIC SL). The artifact score was also significantly decreased (p < 0.0001) with MAVRIC SL compared with 2D FSE for both reviewers. The hip joint capsule and the muscle and tendon attachment sites of the obturator externus and iliopsoas muscles were better depicted with MAVRIC SL than 2D FSE (p < 0.0125). Abnormal findings were significantly better shown on MAVRIC SL imaging compared with 2D FSE imaging (p < 0.0001). CONCLUSION: The MAVRIC SL sequence can significantly reduce metal artifact on 3-T MRI compared with the 2D FSE sequence and can increase diagnostic confidence of 3-T MRI in patients with total HA.

Imaging near metal: The impact of extreme static local field gradients on frequency encoding processes.

PURPOSE: Magnetic resonance imaging capabilities in the direct vicinity of metallic devices have substantially improved with the recent development of three-dimensional multispectral imaging (3D-MSI) methods. When imaging near metallic hardware, the bulk image distortions in 3D-MSI techniques are reduced to the single-pixel level. However, commonly utilized MSI techniques are ultimately limited by frequency-encoding processes and reveal a class of residual intensity-based susceptibility artifacts that have yet to be formally analyzed. METHODS: Empirical measurements and simulation techniques are utilized to study the static local magnetic field gradients induced by metal implants and their general impact on frequency-encoding processes. The specific consequences of these gradients on 3D-MSI approaches are also analyzed using empirical and simulated approaches. RESULTS: Close agreements between empirical and simulated measurements clearly demonstrate the effects of strong local gradients on frequency-encoded imaging capabilities near metallic implants. CONCLUSIONS: 3D-MSI techniques can enable substantially enhanced magnetic resonance imaging capabilities near metallic implants. However, strong local static field gradients generate residual artifacts whose direct mitigation are ultimately limited by frequency encoding processes. Applications of 3D encoding strategies or additional post processing may be required to further reduce residual artifacts in multispectral images near metal implants.

Accelerating sequences in the presence of metal by exploiting the spatial distribution of off-resonance.

PURPOSE: To demonstrate feasibility of exploiting the spatial distribution of off-resonance surrounding metallic implants for accelerating multispectral imaging techniques. THEORY AND METHODS: Multispectral imaging (MSI) techniques perform time-consuming independent three-dimensional acquisitions with varying radio frequency offsets to address the extreme off-resonance from metallic implants. Each off-resonance bin provides a unique spatial sensitivity that is analogous to the sensitivity of a receiver coil and, therefore, provides a unique opportunity for acceleration. Fully sampled MSI was performed to demonstrate retrospective acceleration. A uniform sampling pattern across off-resonance bins was compared with several adaptive sampling strategies using a total hip replacement phantom. Monte Carlo simulations were performed to compare noise propagation of two of these strategies. With a total knee replacement phantom, positive and negative off-resonance bins were strategically sampled with respect to the B0 field to minimize aliasing. Reconstructions were performed with a parallel imaging framework to demonstrate retrospective acceleration. RESULTS: An adaptive sampling scheme dramatically improved reconstruction quality, which was supported by the noise propagation analysis. Independent acceleration of negative and positive off-resonance bins demonstrated reduced overlapping of aliased signal to improve the reconstruction. CONCLUSION: This work presents the feasibility of acceleration in the presence of metal by exploiting the spatial sensitivities of off-resonance bins.

Effects of low-fat and high-fat meals on steady-state pharmacokinetics of lapatinib in patients with advanced solid tumours.

AIM: To quantify the effect of food on the systemic exposure of lapatinib at steady state when administered 1 h before and after meals, and to observe the safety and tolerability of lapatinib under these conditions in patients with advanced solid tumours. METHODS: This was a three-treatment, randomised, three-sequence cross-over study. Lapatinib was administered 1 h after a low- [B] or a high-fat [C] meal and systemic exposure was compared with that obtained following administration 1 h before a low-fat meal [A]. RESULTS: In total, 25 patients were included, of whom 12 were evaluable for the pharmacokinetic analysis. Both low-fat and high-fat meals affected lapatinib exposure. Lapatinib AUC0-24 increased following lapatinib administration 1 h after a low-fat meal by 1.80-fold (90 % CI: 1.37-2.37) and after a high-fat meal by 2.61-fold (90 % CI: 1.98-3.43). Lapatinib Cmax increased following lapatinib administration 1 h after a low-fat meal by 1.90-fold (90 % CI: 1.49-2.43) and after a high-fat meal by 2.66-fold (90 % CI: 2.08-3.41). The most commonly occurring treatment-related toxicity was diarrhoea (8/25, 32 % CTCAE grade 1 and 2/25, 8 % grade 2) and one treatment-related grade ≥ 3 event occurred (fatigue grade 3, 4 %). CONCLUSIONS: Both low-fat and high-fat food consumed 1 h before lapatinib administration increased lapatinib systemic exposure compared with lapatinib administration 1 h before a low-fat meal. In order to administer lapatinib in a fasted state, it is advised to administer the drug 1 h before a meal.

Diffusion Weighted Magnetic Resonance Imaging of Spinal Cord Injuries After Instrumented Fusion Stabilization.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a promising technique for assessing spinal cord injury (SCI) that has historically been challenged by the presence of metallic stabilization hardware. This study leverages recent advances in metal-artifact resistant multi-spectral DW-MRI to enable diffusion quantification throughout the spinal cord even after fusion stabilization. Twelve participants with cervical spinal cord injuries treated with fusion stabilization and 49 asymptomatic able-bodied control participants underwent multi-spectral DW-MRI evaluation. Apparent diffusion coefficient (ADC) values were calculated in axial cord sections. Statistical modeling assessed ADC differences across cohorts and within distinct cord regions of the SCI participants (at, above, or below injured level). Computed models accounted for subject demographics and injury characteristics. ADC was found to be elevated at injured levels compared with non-injured levels (z = 3.2, p = 0.001), with ADC at injured levels decreasing over time since injury (z = -9.2, p < 0.001). Below the injury level, ADC was reduced relative to controls (z = -4.4, p < 0.001), with greater reductions after more severe injuries that correlated with lower extremity motor scores (z = 2.56, p = 0.012). No statistically significant differences in ADC above the level of injury were identified. By enabling diffusion analysis near fusion hardware, the multi-spectral DW-MRI technique allowed intuitive quantification of cord diffusion changes after SCI both at and away from injured levels. This demonstrates the approach's potential for assessing post-surgical spinal cord integrity throughout stabilized regions.

Distinct Functional Connectivity Patterns for Intermittent Vs Constant Neuropathic Pain Phenotypes in Persistent Spinal Pain Syndrome Type 2 Patients.

Background: Chronic low back pain (cLBP) has been associated with alterations in brain functional connectivity (FC) but based upon heterogeneous populations and single network analyses. Our goal is to study a more homogeneous cLBP population and focus on multiple cross-network (CN) connectivity analysis. We hypothesize that within this population: 1) altered CN FC, involving emotion and reward/aversion functions are related to their pain levels and 2) altered relationships are dependent upon pain phenotype (constant neuropathic vs intermittent pain). Methods: In this case series, resting state fcMRI scans were obtained over a study duration of 60 months from 23 patients (13 constant neuropathic and 10 intermittent pain) with Persistent Spinal Pain Syndrome (PSPS Type 2) being considered for spinal cord stimulation (SCS) therapy at a single academic center. Images were acquired using a Discovery MR750 GE scanner. During the resting state acquisitions, they were asked to close their eyes and relax. The CN analysis was performed on 7 brain networks and compared to age-matched controls. Linear regression was used to test the correlation between CN connectivity and pain scores. Results: CN FC involving emotion networks (STM: striatum network index) was significantly lower than controls in all patients, regardless of pain phenotype (P < 0.003). Pain levels were positively correlated with emotional FC for intermittent pain but negatively correlated for constant pain. Conclusion: This is the first report of 1) altered CN FC involving emotion/reward brain circuitry in 2) a homogeneous population of cLBP patients with 3) two different pain phenotypes (constant vs intermittent) in PSPS Type 2 patients being considered for SCS. FC patterns were altered in cLBP patients as compared to controls and were characteristic for each pain phenotype. These data support fcMRI as a potential and objective tool in assessing pain levels in cLBP patients with different pain phenotypes.